| 1 | Circulating extracellular RNAs,myocardial remodeling,and heart failure in patients with acute coronary syndrome显示文摘Background:Given high on-treatment mortality in heart failure(HF),identifying molecular pathways that underlie adverse cardiac remodeling may offer novel biomarkers and therapeutic avenues.Circulating extracellular RNAs(ex-RNAs)regulate important biological processes and are emerging as biomarkers of disease,but less is known about their role in the acute setting,particularly in the setting of HF.Methods:We examined the ex-RNA profiles of 296 acute coronary syndrome(ACS)survivors enrolled in the Transitions,Risks,and Actions in Coronary Events Center for Outcomes Research and Education Cohort.We measured 374 ex-RNAs selected a priori,based on previous findings from a large population study.We employed a two-step,mechanism-driven approach to identify ex-RNAs associated with echocardiographic phenotypes(left ventricular[LV]ejection fraction,LV mass,LV end-diastolic volume,left atrial[LA]dimension,and LA volume index)then tested relations of these ex-RNAs with prevalent HF(N=31,10.5%).We performed further bioinformatics analysis of microRNA(miRNAs)predicted targets’genes ontology categories and molecular pathways.Results:We identified 44 ex-RNAs associated with at least one echocardiographic phenotype associated with HF.Of these 44 exRNAs,miR-29-3p,miR-584-5p,and miR-1247-5p were also associated with prevalent HF.The three microRNAs were implicated in the regulation p53 and transforming growth factor-βsignaling pathways and predicted to be involved in cardiac fibrosis and cell death;miRNA predicted targets were enriched in gene ontology categories including several involving the extracellular matrix and cellular differentiation.Conclusions:Among ACS survivors,we observed that miR-29-3p,miR-584-5p,and miR-1247-5p were associated with both echocardiographic markers of cardiac remodeling and prevalent HF.Relevance for Patients:miR-29c-3p,miR-584-5p,and miR-1247-5p were associated with echocardiographic phenotypes and prevalent HF and are potential biomarkers for adverse cardiac remodeling in HF. | Khanh-Van Tran Kahraman Tanriverdi Gerard P.Aurigemma Darleen Lessard Mayank Sardana Matthew Parker Amir Shaikh Matthew Gottbrecht Zachary Milstone Selim Tanriverdi Olga Vitseva John F.Keaney Catarina I.Kiefe David D.McManus Jane E.Freedman | 2019 | Journal of Clinical & Translational Research2019，5，1： | 7 |
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